Jeong Eun Goo, Lee Sung Hak, Kim Sung Soo, Ahn Chang Hyeok, Yoo Nam Jin, Lee Sug Hyung
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
APMIS. 2007 Aug;115(8):976-81. doi: 10.1111/j.1600-0463.2007.apm_804.x.
Mounting evidence indicates that deregulation of apoptosis contributes to the development of human cancers. BAD, a proapoptotic Bcl-2 family protein, regulates the intrinsic apoptosis pathway. The aim of this study was to explore whether alterations of phospho-BAD (p-BAD) protein that antagonizes apoptosis function of BAD and mutation of BAD gene are characteristics of human gastric cancers. We analyzed expression of p-BAD in 60 gastric adenocarcinomas by immunohistochemistry. Also, we analyzed BAD gene for detection of somatic mutations by single-strand conformation polymorphism (SSCP) assay. p-BAD expression was detected well in normal gastric mucosal epithelial cells, whereas it was detected in only 51% (31 of the 60) of the cancers. There was no somatic mutation of BAD gene in the 60 gastric cancer samples. The decreased expression of p-BAD in malignant gastric epithelial cells compared to normal mucosal epithelial cells suggested that loss of p-BAD expression may play a role in gastric tumorigenesis. The data also suggest that BAD mutation may not be a direct target of inactivation in gastric tumorigenesis.
越来越多的证据表明，细胞凋亡失调与人类癌症的发生发展有关。BAD是一种促凋亡的Bcl-2家族蛋白，可调节内源性凋亡途径。本研究的目的是探讨拮抗BAD凋亡功能的磷酸化BAD（p-BAD）蛋白改变以及BAD基因突变是否为人类胃癌的特征。我们通过免疫组织化学分析了60例胃腺癌中p-BAD的表达。此外，我们采用单链构象多态性（SSCP）分析检测BAD基因的体细胞突变。p-BAD在正常胃黏膜上皮细胞中表达良好，而在仅51%（60例中的31例）的癌症中检测到。60例胃癌样本中未发现BAD基因的体细胞突变。与正常黏膜上皮细胞相比，恶性胃上皮细胞中p-BAD表达降低，提示p-BAD表达缺失可能在胃癌发生中起作用。数据还表明，BAD突变可能不是胃癌发生中失活的直接靶点。
